The cardiac sarcoplasmic reticulum (CSR) represents one of the potential pools of calcium available for activation of contraction. The mechanism of calcium binding by CSR and its possible relation to myocardial relaxation and of calicum release from the CSR as a possible index of activator calcium in normal, failing and ischemic heart has been the major thrust of this grant since its inception. We propose to study calcium accumulation and release and calcium ATPase and factors which influence them. The studies for the present grant period include: 1) Further characterization of nonsteady-state kinetic of calcium metabolism and CSR and their control; 2) Characterization and control of the CSR-glycogen complex as an (internal beta-adrenergic receptor) and an effector site for cyclic AMP mediated functions; and 3) a new project involving isolation and purification of cardiac tubulin from myocardium of adult dogs and assessment of the characteristics of its polymerization, drug binding, calcium interaction, control of other organelle systems, and chemical modification. This latter project stems from the observation that CSR preparations contain large amounts of intact microtubules.